Escherichia coli 0157:H7 is emerging as an important human gastrointestinal pathogen. This organism causes diarrhea, hemorrhagic colitis, and the hemolytic uremic syndrome (HUS). HUS is the most common cause of acute renal failure in childhood in North America, is increasing in incidence, and appears to be an important cause of chronic renal damage. The mechanism whereby E. coli 0157:H7 colonizes the gastrointestinal tracts of humans and cattle, its reservoir, is unknown. This project endeavors to identify and characterize the adhesin through which E. coli 0157:H7 adheres to epithelial cells, which will lead to a better understanding of the biology of gastrointestinal colonization by this pathogen. The long term objective of this project is the prevention or improved treatment of E. coli 0157:H7 infections. The PI will attempt to achieve this objective by preventing colonization or promoting clearance of E. coli 0157:H7 from mucosal surfaces of cattle and humans. To accomplish these objectives, they propose to (1) confirm that the molecule they have cloned and expressed is the adhesin of E. coli O157:H7, (2) study the role of this adhesin in the induction of colitis in rabbits, and in colonization of the gastrointestinal tract of cattle, (3) determine if this adhesin mediates attachment of E. coli 0157:H7 to human gastrointestinal tissue, and determine if infected humans develop antibodies to this molecule, and (4) study the molecular mechanisms underlying the expression of this adhesin in E. coli 0157:H7.